Metabolomics Analysis of Mesenchymal Stem Cells

Various mesenchymal stem cells as easily accessible and multipotent cells can share different essential signaling pathways related to their stemness ability. Understanding the mechanism of stemness ability can be useful for controlling the stem cells for regenerative medicine targets. In this context, OMICs studies can analyze the mechanism of different stem cell properties or stemness ability via a broad range of current high-throughput techniques. This field is fundamentally directed toward the analysis of whole genome (genomics), mRNAs (transcriptomics), proteins (proteomics) and metabolites (metabolomics) in biological samples. According to several studies, metabolomics is more effective than other OMICs ّfor various system biology concerns. Metabolomics can elucidate the biological mechanisms of various mesenchymal stem cell function by measuring their metabolites such as their secretome components. Analyzing the metabolic alteration of mesenchymal stem cells can be useful to promote their regenerative medicine application.

understanding the mechanism of stemness ability is challenging (9). According to several studies, stable, safe, and more accessible stem cells are considered as an excellent choice for regenerative medicine. In this context, mesenchymal stem cells (MSCs) (as easily accessible, self-renewable, and multipotent cells with few consideration ethics) have significant efficacy in regenerative medicine. (12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26). Furthermore, recent development in OMICs approaches (technologies for understanding the whole activity of cells, tissues, and organs at the molecular level) specifically metabolomics approaches (extensive analysis of metabolites in cells, tissues, and organs) can increase our understanding about the self-renewal and differentiation mechanisms. On the other hand, analysis of chemical alterations related to natural processes of living cells including growth, environmental adaptation, and differentiation can be provided by metabolomics methods (27)(28)(29).

OMICs -based stem cell monitoring
Multi-OMICs approaches including genomics, epigenomics, transcriptomics, proteomics, and metabolomics are functional methods to study stem cell biology and its therapeutic application  At first, human genome project has led to the advancement of genome sequencing and study on DNA by analysis of single nucleotide polymorphisms (SNPs), variation copies, and mutations (34)(35)(36). Nowadays, genomics as the most mature approache of OMICs and next generation sequencing (NGS) as the latest technology in this field are used for highthroughput detection and cost effective analysis of biological data (37)(38)(39)(40). On the other hand, epigenetic modifications (e.g. methylation and histone acetylation) have an important role in differentiation and development of stem cells (41,42). The study of heritable modifications (not sequence changes) of DNA is called epigenomics (43,44). Additionally, qualitative and quantitative transcriptomics can facilitate the investigation of RNAs in stem cells, via molecular and cellular methods such as micro-array and RNA-sequencing (45,46). It also has a vital role in analyzing key genes and pathways that participate in self-renewal, proliferation, and differentiation of stem cells (47)(48)(49). Some transcription factors (related to noncoding RNAs) such as octamer-binding transcription factor 4 (OCT 4) and NANOG can regulate pluripotency feature of stem cells (50,51).
Proteomics tries to evaluate the qualitative and quantitative changes in proteins and identify new markers in stem cell development stages (52,53).
Finally, metabolomics measures and demonstrates the products of metabolism such as amino-acids and fatty-acids. In this respect, metabolomics is an accurate approach to recognize metabolite biomarkers in biological samples (54,55).
Although, application of OMICs, especially metabolomics, for monitoring of stem cell in researches and therapies is in its infancy period, it can be useful to understand different features of cell-based therapy (1,56).

Stem cells metabolomics
Because of the self-renewal and differentiation properties of stem cells, they can be applied for regenerative medicine, drug screening, toxicity testing, and evaluation of disease phenotypes (57)(58)(59) Moreover, the increase of reactive oxygen species (ROS) can promote cell differentiation (74,79).
Herein, understanding the mechanism of stem cells   (99).

Conclusion and future perspectives
Metabolomics is an impressive research area, which can be used for screening the metabolic modifications during the stem cells reprogramming, proliferation, and differentiation (56,115